Memory of Chirality of Tertiary Aromatic Amide: Application to the Asymmetric Synthesis of (S)-α-MethylDOPA

Abstract

We describe an original asymmetric synthesis of (S)-α-methylDOPA proceeding by the concept of memory of chirality, the only source of chirality being the starting D-alanine. The initial chirality of the amino acid is temporarily transferred to a dynamic axial chirality of a tertiary aromatic amide. The (S)-α-methylDOPA hydrochloride is obtained after four steps with 98% ee.

Recent Progress in Memory Of Chirality (MOC): An Advanced Chiral Pool

“…This strategy was applied to the synthesis of L-meth-ylDOPA hydrochloride, used for the treatment for hyperten-sion. 65 Overall four steps were required for the synthesis because the deprotection procedure via the two-step sequence involving basic hydrolysis of the oxazolidinone followed by complete hydrolysis under acidic conditions was preferable to avoid the Pictet-Spengler-type side reaction (Scheme 36).…”

Memory of Chirality in a Flow‐Based System: Enantioselective Synthesis of Quaternary α‐Amino Acids Using Flow Microreactors

“…Therefore this strategy is very sensitive to reaction conditions in particular reaction rate and temperature, and many MOC reactions are either intramolecular or performed at low temperature or both , . We have already developed a 3‐step asymmetric synthesis of quaternary α‐amino acids based on MOC . The key step is an intermolecular alkylation of an enolate and the initial chirality of the starting α‐amino acid is “memorized” at only low temperatures by a chiral conformation of a tertiary aromatic amide (Scheme ).…”

Synthesis of Organometallic Compounds in Flow

“…Based on their previous works on Memory of Chirality (MOC) they developed a flow process for the generation of quaternary stereocenters with high selectivity. Chiral enolates, prepared using LDA, reacted with different electrophiles ( Figure ), leading to alkylations with an efficient memory of chirality.…”